Rethinking white matter-tumor interaction: a tractography based analysis of associations between fractional anisotropy and morphometry in the IFOF and arcuate fasciculus

Background: White matter (WM) tract involvement represents a critical determinant of functional outcome in neuro-oncology. Although substantial advances in diffusion tensor imaging (DTI) and intraoperative mapping have improved characterization of WM organization, the relationship between microstructural integrity and morphometric alterations of associative fasciculi in different tumor histotypes remains incompletely understood. We investigated the association between fractional anisotropy (FA), volumetric and length parameters of the inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus (AF) across distinct intracranial tumor types. Methods: In this multicenter retrospective study, 156 patients undergoing surgery for brain tumors were included. All lesions were located in proximity to the IFOF or AF and underwent preoperative deterministic tractography based on standardized DTI protocols. Linear mixed-effects models, adjusted for relevant covariates, assessed the association between FA and tract morphometry, including interaction terms for tumor type and hemisphere. Results: Higher FA was strongly associated with both AF and IFOF tract volume (adjusted p < 0.001), whereas associations with tract length were weaker and not consistently significant. The association between FA and IFOF volume appeared stronger in gliomas than in metastases or meningiomas, suggesting potential histotype-related difference in WM involvement. The healthy hemisphere showed higher FA and morphometric measures than the tumor-affected side. Conclusions: FA was significantly associated with morphometric features of WM tract, particularly in infiltrative tumors. Integrating FA into preoperative assessment may enhance surgical planning and support strategies aimed at preserving functional connectivity.